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Gordon Townsend tells his two young daughters Amy and Kim that he and their mother are divorcing because monogamy is not realistic, repeating it like a mantra. Twenty-three years later, Amy is a party girl who drinks too much and sleeps around while writing for a men's magazine. She is in a casual relationship with a gym-addict named Steven, who was attracted to her because he first thought she 'looked like a dude'. Her cold-hearted English boss, Dianna, assigns her to write an article about a sports doctor named Aaron Conners.

While Amy is interviewing Aaron, she receives a text from Kim insisting they move Gordon to a cheaper facility. Amy starts to hyperventilate, but Aaron calms her down and suggests they get food. Over dinner, he compliments her writing and she learns about his family. After some drinks, they go to his place and have sex together. Amy stays the night, which is a departure from her rule of never sleeping over with a man she's had sex with.

The next day, Aaron calls to ask if they can see each other again. Amy panics and tells him they will talk about it at the interview. She and her friend Nikki decide she has to end it. Meanwhile, Aaron's friend, LeBron James, is excited for him since Aaron has not dated anyone in six years. Amy goes to watch Aaron perform surgery to "Uptown Girl", his favorite song. Afterwards, she tries to break things off. He insists they like each other and should date. Amy then gets a phone call that her dad had a fall. Aaron drives her to the home where he tends to her dad.

Aaron and Amy begin dating and fall for each other. Amy is worried she is going to mess up the relationship, but Kim tells her she is just doing what everyone else does. Gordon avoids taking his medication and dies. At his funeral, Aaron tells her, for the first time, that he loves her. She tells him that it was the wrong time for him to start saying that to her.

Aaron receives a prestigious award at a luncheon and brings Amy. While making his speech, Amy gets a call from her boss Dianna, who threatens to fire her if she does not answer. She chooses to take the call and leaves during his speech. Afterwards, Aaron is upset and they start arguing. They return to her apartment, but Aaron thinks they should not go to bed angry, so Amy rants all night. The next day Aaron tells Amy that they need to take a break. Hurt, Amy reacts by telling him that it is fine.

Amy goes out drinking with her co-workers, including an intern, who invites her back to his place; their bizarre sexual encounter is interrupted when his mom enters and reveals that he is only 16. The next day, Dianna fires Amy for the incident. Aaron is moping in his apartment until LeBron calls, claiming he has been injured. Aaron rushes over to find an intervention for him consisting of LeBron, Matthew Broderick, Chris Evert, and Marv Albert. They tell him he has always been afraid of opening up and needs to make things right with Amy, but Aaron insists things with Amy are over.

Amy visits Kim and tells her everything that has happened; Kim tells her that it's time to change. Amy clears out all the alcohol from her apartment. She takes her Aaron story to Vanity Fair, where it ends up getting published, and sends it to Aaron. He attends a game and after, Aaron is called back to the court, where the Knicks City Dancers perform with Amy front and center. She tells him she wants to make their relationship work. They confess their love for each other and kiss.

Trainwreck grossed $110.2 million in North America and $30.6 million in other territories for a total gross of $140.8 million, against a budget of $35 million.[3]

In the United States and Canada, Trainwreck opened on July 17, 2015, the same day as the superhero film Ant-Man. Initial projections had the film opening to around $20 million, with The Hollywood Reporter noting that it could overperform if it takes off among females or underperform given how R-rated comedies have struggled over the summer, with both Ted 2 and Magic Mike XXL failing to meet expectations.[2] It made $1.8 million on Thursday night showings, which began at 8 p.m. from 2,363 theaters,[24] and $10.7 million on its opening day.[25] Through its opening weekend, it grossed $30.1 million from 3,158 theaters, exceeding expectations. This was Apatow's second biggest debut as a director (just behind the $30.7 million debut of Knocked Up) and the sixth-biggest debut for a film that he was involved in as a writer, director or producer.[26][27][28] The film played 69% female with 66% over 25 years old which is typical for an R-rated comedy. According to a poll conducted by Rentrak in its opening weekend, 28% of respondents said they went to see the film because of Schumer.[26]

On Rotten Tomatoes the film has an approval rating of 85% based on 236 reviews with an average rating of 7.1/10. The site's critical consensus reads, "Trainwreck drags commitment out of all but the most rom-com-phobic filmgoers with sharp humor, relatable characters, and hilarious work from Amy Schumer."[29] On Metacritic, the film has a score of 75 out of 100 based on 45 critics, indicating "generally favorable reviews".[30] Audiences polled by CinemaScore gave the film an average grade of "A-" on an A+ to F scale.[31]

Michael Phillips of the Chicago Tribune gave the film three and a half stars out of four, saying "Schumer and Hader are wonderful together. Gender inequity in the world of comedy deserves all the overdue attention it's getting, and more. But there are matters of craft, wit (no matter how crude the jokes) and timing that transcend chromosomes."[32]Richard Roeper of The Chicago Sun Times praised the performances of the cast, particularly Schumer, Hader, Quinn, and James.[33] He also called Schumer's performance worthy of an Academy Award nomination.[34] Benjamin Lee of The Guardian gave the film three out of five stars, stating, "Judd Apatow's latest is rough around the edges, but his focus on a female protagonist refreshes a genre in sore need of change".[35] Ian Crouch, writing for The New Yorker, singled out LeBron James' performance for praise, writing that "it seems safe to declare that he has given the greatest motion-picture acting performance by an active professional basketball player of all time."[36] Chris Nashawaty of Entertainment Weekly gave the film a B+, saying "Beneath all of his bad-boy shtick, Apatow's always been a pretty conventional moralist. But Schumer gives their raunchy rom-com enough of her signature spikiness to prevent it from ever feeling predictable."[37] Jacob Hall of the New York Daily News gave the film four out of five stars, saying "Schumer raises Apatow's game beautifully. Her biting, pitch-black wit and his penchant for character-driven comedy go together like gin and tonic."[38]Peter Travers of Rolling Stone gave the film three and a half stars out of four, saying "Sweet is not how Schumer wants Trainwreck to go down. She wants to explode rom-com clichés and replace them with something fierce and ready to rumble. Done."[39]

Sara Stewart of the New York Post gave the film four out of four stars, saying "Trainwreck is a corrective to a lot of outdated clichés. It's very funny and sweet and even a little weepy, and it has maybe the best scene ever filmed of dirty talk gone wrong."[40] Ty Burr of The Boston Globe gave the film three out of four stars, saying "Trainwreck serves as confirmation that a star is born, a seemingly average woman whose above-average superpowers include reminding us of our own. Where she goes from here should be fascinating to watch."[41] Brian Truitt of USA Today gave the film three out of four stars, saying "With films such as Funny People and This Is 40, Apatow has toyed with finding the right blend of the serious and the hilarious and finally hits it here."[42] Moira MacDonald of The Seattle Times gave the film three out of four stars, saying "There's nothing remotely fresh about this plotline (or the way Apatow, true to form, makes the movie 20 minutes longer than it should be), but Trainwreck works as comedy more often than it doesn't – and that's rare enough."[43] Alonso Duralde of The Wrap said, "Ultimately comes down in favor of mainstream girl-gets-boy in a way that Inside Amy Schumer might find a little dubious, but it never feels like Schumer is aggressively watering down her uniquely prickly brand of comedy for a mass audience."[44]

On July 23, 2015, a shooting occurred at The Grand 16 Theater movie theater in Lafayette, Louisiana, during a showing of Trainwreck.[45] John Russell Houser, age 59,[46][47] opened fire during a showing of the film, killing two people and injuring nine others before he committed suicide.[48][49][50][51]

Schumer posted on her Twitter account: "My heart is broken and all my thoughts and prayers are with everyone in Louisiana."[52]Universal Studios, the film's distributor, also released a statement: "All of us at Universal Pictures send our heartfelt sympathies to the victims of this senseless tragedy and their families in Louisiana."[53]

After the tragedy, Schumer advocated for stricter gun control laws with New York Senator Chuck Schumer, to whom she is related. In October 2015, three months after the shooting, Schumer dedicated her HBO stand-up special Amy Schumer: Live at the Apollo to her niece and the two victims of the shooting.[54]